The periodontal tissue is composed of alveolar bone, periodontal ligament and gingiva (gum). The alveolar bone is attached firmly to the basal bone of the jaw bone, and is the 2-3 mm region adjacent to the dental root, but usually is all of the scleroid tissue including the above alveolar bone. Alveolar bone lowers down as human ages, sometimes exposing the root of the tooth. Also loss of a tooth can cause the loss of alveolar bone. The alveolar bone and tooth are attached by periodontal ligament, which has undifferentiated mesenchymal cells, with an average thickness of 0.2 mm. Alveolar bone buffers and distributes the force when chewing food, and sends the sensation of tooth to the alveolar bone by way of periodontal ligaments. Also, the periodontal ligament is a layer with undifferentiated mesenchymal cells and is structured for bone remodeling and adapted to pressure without losing the structure and function of whole fiber. The undifferentiated mesenchymal cells inside the periodontal ligament move to adjacent tissues. The cells move to the alveolar bone for bone remodeling and to teeth for holding them tight by forming collagen fiber continuously.
Gingiva is a part of supporting tissues that can be seen from outside in the mouth, and usually is a starting point of the disease (gingivitis). When the disease spreads into the supporting tissues, root surface and the periodontal ligament attached to the bone tissue around the tooth are destroyed causing subsequent destruction of alveolar bone to cause periodontal disease.
Periodontal disease is one of the most frequently occurring diseases in the oral cavity alongside with dental caries with the clinical symptoms of gingival bleeding, glossoncus, formation of periodontal pocket, loss of attached gingiva, alveolar bone destruction and ozostomia and a major cause of tooth loss (Ali, R. W. et al., J. Clin. Periodontol. 1997, 24, 830-835; Socransky, S. S. et al., J. Clin. Periodontol. 1998, 15, 440-444). Periodontal disease is one of the generally occurring chronic disease caused by inflammation, and about 10 to 60% of adults have the disease with various diagnostic stages (Xiong, X. et al., BJOG. 2006, 113, 135-143; Albandar, J. M. and T. E. Rams, Periodontol. 2000, 2002, 29, 7-10).
The types of periodontal disease include gingivitis with inflammation in the soft tissue and gingiva and periodontitis with destruction of supporting tissue of the periodontal ligament, alveolar bone, caries of cementum and soft tissues (Kinane D. F., Periodontol. 2000, 2001, 25, 8-20). Periodontal disease, which can incur the tooth loss, is a disease by bacterial infection and is caused by the microorganisms and the their secretion inducing inflammation coexisting in the biofilms called dental plaque (Feng, Z., and A. Weinberg, Periodontol. 2000, 2006, 40, 50-76).
As people age, periodontal disease such as periodontitis or alveolar osteochondrodyslpasia can be caused when the alveolar bones weakens by congenital or acquired reasons. The above alveolar osteochondrodyslpasia can cause tooth loss due to alveolar osteoporosis, alveolar osteomalacia, and alveolar bone loss. Alveolar bone maintains itself by remodeling including osteogenesis by osteoblast and osteolysis by osteoclast. These metabolism is controlled by the hormonal system and local factors, and alveolar osteochondrodyslpasia such as alveolar osteoporosis can be caused when the bone mass decreased below limitations by excessive osteolysis than osteogenesis. Osteoblast can help osteogenesis by precipitating the organic material in the bone, osteoid, which is composed of type 1 collagen, osteocalcin, osteonectin and sialoprotein. Formed osteoid later go through mineralization in which the osteoblast induce the mineralization of forming hydroxyapatite, a crystallite of calcium phosphate, to be precipitated to osteoid.
There has been increasing reports showing the relationship between periodontal disease and systemic diseases including arteriosclerosis, heart attack, stroke, diabetes and pregnancy complications (Desvarieux, M. et al., Circulation, 2005, 111, 576-582; Offenbacher, S. et al., J. Periodontol., 1996, 67, 1103-1113; Garcia, R. I. et al., Periodontol. 2000, 2001, 25, 21-36; Champagne, C. M. et al., J. Int. Acad. Periodontol., 2000, 2, 9-13; Paquette, D. W., J. Int., Acad. Periodontol., 2002, 4, 101-119). And pregnancy complications related to periodontal diseases are reported to be premature birth, low birth weight, miscarriage and preeclampsia (McCormick, M. C., N. Engl. J. Med., 1985, 312, 82-90; Shennan, A. H., BMJ, 2003, 327, 604-618). Therefore, it is most important to develop effective drugs for periodontal disease since it is a big threat for public health.
Improvement of oral hygiene, non-surgical and surgical treatments (scaling, root planing, curettage and alveolar tissue regeneration), and the like are used for the treatment of periodontal disease. Since surgical method, the most effective treatment, is cumbersome due to hospital visitation and has limitations of being done after development of the disease, periodontal disease becomes a chronic disease. Antibiotics or local sustained release formulations have been used as additive therapy, but the drugs go to unnecessary parts of the body causing side-effects such as resistance. Recently resistant microorganism of periodontal disease has been identified.
To overcome the limitations of the above surgical therapy and use of antibiotics and to improve the prevention and therapeutic effects, development of new drug with anti-inflammatory activity and ability to recover the alveolar tissues from destruction and loss is needed.